Differential methylation at the RELN gene promoter in temporal cortex from autistic and typically developing post-puberal subjects

Carla Lintas, Roberto Sacco, Antonio M. Persico

Research output: Contribution to journalArticle

Abstract

Background: Reelin plays a pivotal role in neurodevelopment and in post-natal synaptic plasticity and has been implicated in the pathogenesis of autism spectrum disorder (ASD). The reelin (RELN) gene expression is significantly decreased in ASD, both in the brain and peripherally. Methylation at the RELN gene promoter is largely triggered at puberty, and hypermethylation has been found in post-mortem brains of schizophrenic and bipolar patients. Methods: In this study, we assessed RELN gene methylation status in post-mortem temporocortical tissue samples (BA41/42 or 22) of six pairs of post-puberal individuals with ASD and typically developing subjects, matched for sex (male:female, M:F = 5:1), age, and post-mortem interval. Results: ASD patients display a significantly higher number of methylated CpG islands and heavier methylation in the 5′ region of the RELN gene promoter, spanning from -458 to -223 bp, whereas controls have more methylated CpG positions and greater extent of methylation at the 3′ promoter region, spanning from -222 to +1 bp. The most upstream promoter region (-458 to -364 bp) is methylated only in ASD brains, while the most downstream region (-131 to +1 bp) is methylated exclusively in control brains. Within this general framework, three different methylation patterns are discernible, each correlated with different extents of reduction in reelin gene expression among ASD individuals compared to controls. Conclusions: The methylation pattern is different in ASD and control post-mortem brains. ASD-specific CpG positions, located in the most upstream gene promoter region, may exert a functional role potentially conferring ASD risk by blunting RELN gene expression.

Original languageEnglish
Article number9151
JournalJournal of Neurodevelopmental Disorders
Volume8
Issue number1
DOIs
Publication statusPublished - Apr 29 2016
Externally publishedYes

Fingerprint

Temporal Lobe
Methylation
Genes
Genetic Promoter Regions
Brain
Gene Expression
Autism Spectrum Disorder
CpG Islands
Neuronal Plasticity
Puberty

Keywords

  • Autism
  • DNA methylation
  • Epigenetics
  • Post-mortem brains
  • Reelin

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Cognitive Neuroscience
  • Pediatrics, Perinatology, and Child Health

Cite this

Differential methylation at the RELN gene promoter in temporal cortex from autistic and typically developing post-puberal subjects. / Lintas, Carla; Sacco, Roberto; Persico, Antonio M.

In: Journal of Neurodevelopmental Disorders, Vol. 8, No. 1, 9151, 29.04.2016.

Research output: Contribution to journalArticle

@article{67e60387c8734d2b904ccfc042e1eac2,
title = "Differential methylation at the RELN gene promoter in temporal cortex from autistic and typically developing post-puberal subjects",
abstract = "Background: Reelin plays a pivotal role in neurodevelopment and in post-natal synaptic plasticity and has been implicated in the pathogenesis of autism spectrum disorder (ASD). The reelin (RELN) gene expression is significantly decreased in ASD, both in the brain and peripherally. Methylation at the RELN gene promoter is largely triggered at puberty, and hypermethylation has been found in post-mortem brains of schizophrenic and bipolar patients. Methods: In this study, we assessed RELN gene methylation status in post-mortem temporocortical tissue samples (BA41/42 or 22) of six pairs of post-puberal individuals with ASD and typically developing subjects, matched for sex (male:female, M:F = 5:1), age, and post-mortem interval. Results: ASD patients display a significantly higher number of methylated CpG islands and heavier methylation in the 5′ region of the RELN gene promoter, spanning from -458 to -223 bp, whereas controls have more methylated CpG positions and greater extent of methylation at the 3′ promoter region, spanning from -222 to +1 bp. The most upstream promoter region (-458 to -364 bp) is methylated only in ASD brains, while the most downstream region (-131 to +1 bp) is methylated exclusively in control brains. Within this general framework, three different methylation patterns are discernible, each correlated with different extents of reduction in reelin gene expression among ASD individuals compared to controls. Conclusions: The methylation pattern is different in ASD and control post-mortem brains. ASD-specific CpG positions, located in the most upstream gene promoter region, may exert a functional role potentially conferring ASD risk by blunting RELN gene expression.",
keywords = "Autism, DNA methylation, Epigenetics, Post-mortem brains, Reelin",
author = "Carla Lintas and Roberto Sacco and Persico, {Antonio M.}",
year = "2016",
month = "4",
day = "29",
doi = "10.1186/s11689-016-9151-z",
language = "English",
volume = "8",
journal = "Journal of Neurodevelopmental Disorders",
issn = "1866-1947",
publisher = "Springer New York",
number = "1",

}

TY - JOUR

T1 - Differential methylation at the RELN gene promoter in temporal cortex from autistic and typically developing post-puberal subjects

AU - Lintas, Carla

AU - Sacco, Roberto

AU - Persico, Antonio M.

PY - 2016/4/29

Y1 - 2016/4/29

N2 - Background: Reelin plays a pivotal role in neurodevelopment and in post-natal synaptic plasticity and has been implicated in the pathogenesis of autism spectrum disorder (ASD). The reelin (RELN) gene expression is significantly decreased in ASD, both in the brain and peripherally. Methylation at the RELN gene promoter is largely triggered at puberty, and hypermethylation has been found in post-mortem brains of schizophrenic and bipolar patients. Methods: In this study, we assessed RELN gene methylation status in post-mortem temporocortical tissue samples (BA41/42 or 22) of six pairs of post-puberal individuals with ASD and typically developing subjects, matched for sex (male:female, M:F = 5:1), age, and post-mortem interval. Results: ASD patients display a significantly higher number of methylated CpG islands and heavier methylation in the 5′ region of the RELN gene promoter, spanning from -458 to -223 bp, whereas controls have more methylated CpG positions and greater extent of methylation at the 3′ promoter region, spanning from -222 to +1 bp. The most upstream promoter region (-458 to -364 bp) is methylated only in ASD brains, while the most downstream region (-131 to +1 bp) is methylated exclusively in control brains. Within this general framework, three different methylation patterns are discernible, each correlated with different extents of reduction in reelin gene expression among ASD individuals compared to controls. Conclusions: The methylation pattern is different in ASD and control post-mortem brains. ASD-specific CpG positions, located in the most upstream gene promoter region, may exert a functional role potentially conferring ASD risk by blunting RELN gene expression.

AB - Background: Reelin plays a pivotal role in neurodevelopment and in post-natal synaptic plasticity and has been implicated in the pathogenesis of autism spectrum disorder (ASD). The reelin (RELN) gene expression is significantly decreased in ASD, both in the brain and peripherally. Methylation at the RELN gene promoter is largely triggered at puberty, and hypermethylation has been found in post-mortem brains of schizophrenic and bipolar patients. Methods: In this study, we assessed RELN gene methylation status in post-mortem temporocortical tissue samples (BA41/42 or 22) of six pairs of post-puberal individuals with ASD and typically developing subjects, matched for sex (male:female, M:F = 5:1), age, and post-mortem interval. Results: ASD patients display a significantly higher number of methylated CpG islands and heavier methylation in the 5′ region of the RELN gene promoter, spanning from -458 to -223 bp, whereas controls have more methylated CpG positions and greater extent of methylation at the 3′ promoter region, spanning from -222 to +1 bp. The most upstream promoter region (-458 to -364 bp) is methylated only in ASD brains, while the most downstream region (-131 to +1 bp) is methylated exclusively in control brains. Within this general framework, three different methylation patterns are discernible, each correlated with different extents of reduction in reelin gene expression among ASD individuals compared to controls. Conclusions: The methylation pattern is different in ASD and control post-mortem brains. ASD-specific CpG positions, located in the most upstream gene promoter region, may exert a functional role potentially conferring ASD risk by blunting RELN gene expression.

KW - Autism

KW - DNA methylation

KW - Epigenetics

KW - Post-mortem brains

KW - Reelin

UR - http://www.scopus.com/inward/record.url?scp=84964720192&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84964720192&partnerID=8YFLogxK

U2 - 10.1186/s11689-016-9151-z

DO - 10.1186/s11689-016-9151-z

M3 - Article

AN - SCOPUS:84964720192

VL - 8

JO - Journal of Neurodevelopmental Disorders

JF - Journal of Neurodevelopmental Disorders

SN - 1866-1947

IS - 1

M1 - 9151

ER -